The Use of Ranolazine to Facilitate Electrical Cardioversion in Cardioversion‐Resistant Patients: A Case Series

Murdock, David K.; Kaliebe, Jeff; Larrain, Germán

doi:10.1111/j.1540-8159.2011.03298.x

Cited by 52 publications

(38 citation statements)

References 36 publications

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“…Subsequently, a number of small exploratory clinical studies showed the effectiveness of ranolazine to terminate paroxysmal AF [81, 82] and prevent post-operative AF [83]. Ranolazine has been shown also to facilitate electrical cardioversion of AF in cardioversion-resistant patients [84] as well as to improve effectiveness of amiodarone to terminate paroxysmal AF [85]. …”

Section: Anti-arrhythmic Efficacy Of Late Sodium Current Inhibitionmentioning

confidence: 99%

Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation

Burashnikov

Antzelevitch

2012

Cardiovasc Drugs Ther

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The anti-arrhythmic efficacy of the late sodium channel current (late INa) inhibition has been convincingly demonstrated in the ventricles, particularly under conditions of prolonged ventricular repolarization. The value of late INa block in the setting of atrial fibrillation (AF) remains poorly investigated. All sodium channel blockers inhibit both peak and late INa and are generally more potent in inhibiting late vs. early INa. Selective late INa block does not prolong the effective refractory period (ERP), a feature common to practically all anti-AF agents. Although the late INa blocker ranolazine has been shown to be effective in suppression of AF, it is noteworthy that at concentrations at which it blocks late INa in the ventricles, it also potently blocks peak INa in the atria, thus causing rate-dependent prolongation of ERP due to development of post-repolarization refractoriness. Late INa inhibition in atria is thought to suppress intracellular calcium (Cai)-mediated triggered activity, secondary to a reduction in intracellular sodium (Nai). However, agents that block late INa (ranolazine, amiodarone, vernakalant, etc) are also potent atrial-selective peak INa blockers, so that the reduction of Nai loading in atrial cells by these agents can be in large part due to the block of peak INa. The impact of late INa inhibition is reduced by the abbreviation of the action potential that occurs in AF patients secondary to electrical remodeling. It stands to reason that selective late INa block may contribute more to inhibition of Cai-mediated triggered activity responsible for initiation of AF in clinical pathologies associated with a prolonged atrial APD (such as long QT syndrome). Additional studies are clearly needed to test this hypothesis.

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Section: Anti-arrhythmic Efficacy Of Late Sodium Current Inhibitionmentioning

confidence: 99%

Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation

Burashnikov

Antzelevitch

2012

Cardiovasc Drugs Ther

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“…A small-scale study of patients with new onset or paroxysmal atrial fibrillation (AF; most of whom had some structural heart disease) showed 72% (13/18 patients) conversion to sinus rhythm with high dose (2000 mg) ranolazine, suggesting that further evaluation of ranolazine for AF conversion is warranted [20]. A study of 25 patients with AF resistant to electrical cardioversion, found that 19 patients were successfully cardioverted within two attempts, following oral ranolazine administration [21].…”

Section: Introductionmentioning

confidence: 99%

Ranolazine inhibition of hERG potassium channels: Drug–pore interactions and reduced potency against inactivation mutants

Zhang

Harchi

et al. 2014

Journal of Molecular and Cellular Cardiology

101

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The antianginal drug ranolazine, which combines inhibitory actions on rapid and sustained sodium currents with inhibition of the hERG/IKr potassium channel, shows promise as an antiarrhythmic agent. This study investigated the structural basis of hERG block by ranolazine, with lidocaine used as a low potency, structurally similar comparator. Recordings of hERG current (IhERG) were made from cell lines expressing wild-type (WT) or mutant hERG channels. Docking simulations were performed using homology models built on MthK and KvAP templates. In conventional voltage clamp, ranolazine inhibited IhERG with an IC50 of 8.03 μM; peak IhERG during ventricular action potential clamp was inhibited ~ 62% at 10 μM. The IC50 values for ranolazine inhibition of the S620T inactivation deficient and N588K attenuated inactivation mutants were respectively ~ 73-fold and ~ 15-fold that for WT IhERG. Mutations near the bottom of the selectivity filter (V625A, S624A, T623A) exhibited IC50s between ~ 8 and 19-fold that for WT IhERG, whilst the Y652A and F656A S6 mutations had IC50s ~ 22-fold and 53-fold WT controls. Low potency lidocaine was comparatively insensitive to both pore helix and S6 mutations, but was sensitive to direction of K+ flux and particularly to loss of inactivation, with an IC50 for S620T-hERG ~ 49-fold that for WT IhERG. Docking simulations indicated that the larger size of ranolazine gives it potential for a greater range of interactions with hERG pore side chains compared to lidocaine, in particular enabling interaction of its two aromatic groups with side chains of both Y652 and F656. The N588K mutation is responsible for the SQT1 variant of short QT syndrome and our data suggest that ranolazine is unlikely to be effective against IKr/hERG in SQT1 patients.

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“…A trend for reduced episodes of new‐onset AF was already mentioned in MERLIN‐TIMI 36 trial 14. Several subsequent reports highlight the positive effect of ranolazine against atrial fibrillation in specific populations: post‐CABG, for the conversion of recent‐onset atrial fibrillation or in cardioversion‐resistant patients 15, 22, 23, 24, 25, 26, 27, 28. Moreover, RAFFAELLO trial 29 demonstrated that ranolazine in doses of 500 and 750 mg reduced AF recurrences compared to placebo (borderline significance).…”

Section: Discussionmentioning

confidence: 86%

Ranolazine: safe and effective in a patient with hypertensive cardiomyopathy and multiple episodes of electrical storm

Margos

Mokadem

et al. 2017

Clinical Case Reports

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Key Clinical MessageAmong implantable cardioverter‐defibrillator (ICD) recipients, there are patients with recurrent episodes of electrical storm (ES), retractable to the optimal antiarrhythmic drug therapy or invasive ablation procedures. A relatively novel anti‐ischemic drug with also antiarrhythmic properties, ranolazine, may effectively suppress ventricular arrhythmias in such patients for a long period of time.

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The Use of Ranolazine to Facilitate Electrical Cardioversion in Cardioversion‐Resistant Patients: A Case Series

Abstract: RZ shows promise as a safe and convenient agent to facilitate EC in EC-resistant patients. It appears to be most effective in patients whose AF duration is known to be less than 3 months.

Cited by 52 publications

References 36 publications

Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation

Role of Late Sodium Channel Current Block in the Management of Atrial Fibrillation

Ranolazine inhibition of hERG potassium channels: Drug–pore interactions and reduced potency against inactivation mutants

Ranolazine: safe and effective in a patient with hypertensive cardiomyopathy and multiple episodes of electrical storm

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